Cell host & microbe最新文献

From poo to promise: Fecal microbiota transplants support immunotherapy re-sensitization in solid tumors. 从 "便便 "到 "希望"：粪便微生物群移植支持实体瘤免疫疗法的再敏感化。

Cell host & microbe Pub Date : 2024-08-14 DOI: 10.1016/j.chom.2024.07.015

Laura Chambers, Dennis Grencewicz, Daniel Spakowicz

引用次数: 0

Brucella-driven host N-glycome remodeling controls infection. 布鲁氏菌驱动的宿主 N-糖蛋白重塑控制着感染。

Cell host & microbe Pub Date : 2024-04-10 Epub Date: 2024-03-25 DOI: 10.1016/j.chom.2024.03.003

Ana-Lucia Cabello, Kelsey Wells, Wenjing Peng, Hui-Qiang Feng, Junyao Wang, Damien F Meyer, Christophe Noroy, En-Shuang Zhao, Hao Zhang, Xueqing Li, Haowu Chang, Gabriel Gomez, Yuxin Mao, Kristin L Patrick, Robert O Watson, William K Russell, Aiying Yu, Jieqiang Zhong, Fengguang Guo, Mingqian Li, Mingyuan Zhou, Xiaoning Qian, Koichi S Kobayashi, Jianxun Song, Suresh Panthee, Yehia Mechref, Thomas A Ficht, Qing-Ming Qin, Paul de Figueiredo

{"title":"Brucella-driven host N-glycome remodeling controls infection.","authors":"Ana-Lucia Cabello, Kelsey Wells, Wenjing Peng, Hui-Qiang Feng, Junyao Wang, Damien F Meyer, Christophe Noroy, En-Shuang Zhao, Hao Zhang, Xueqing Li, Haowu Chang, Gabriel Gomez, Yuxin Mao, Kristin L Patrick, Robert O Watson, William K Russell, Aiying Yu, Jieqiang Zhong, Fengguang Guo, Mingqian Li, Mingyuan Zhou, Xiaoning Qian, Koichi S Kobayashi, Jianxun Song, Suresh Panthee, Yehia Mechref, Thomas A Ficht, Qing-Ming Qin, Paul de Figueiredo","doi":"10.1016/j.chom.2024.03.003","DOIUrl":"10.1016/j.chom.2024.03.003","url":null,"abstract":"Many powerful methods have been employed to elucidate the global transcriptomic, proteomic, or metabolic responses to pathogen-infected host cells. However, the host glycome responses to bacterial infection remain largely unexplored, and hence, our understanding of the molecular mechanisms by which bacterial pathogens manipulate the host glycome to favor infection remains incomplete. Here, we address this gap by performing a systematic analysis of the host glycome during infection by the bacterial pathogen Brucella spp. that cause brucellosis. We discover, surprisingly, that a Brucella effector protein (EP) Rhg1 induces global reprogramming of the host cell N-glycome by interacting with components of the oligosaccharide transferase complex that controls N-linked protein glycosylation, and Rhg1 regulates Brucella replication and tissue colonization in a mouse model of brucellosis, demonstrating that Brucella exploits the EP Rhg1 to reprogram the host N-glycome and promote bacterial intracellular parasitism, thereby providing a paradigm for bacterial control of host cell infection.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"588-605.e9"},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human cytomegalovirus degrades DMXL1 to inhibit autophagy, lysosomal acidification, and viral assembly. 人类巨细胞病毒会降解 DMXL1，从而抑制自噬、溶酶体酸化和病毒组装。

Cell host & microbe Pub Date : 2024-04-10 Epub Date: 2024-03-12 DOI: 10.1016/j.chom.2024.02.013

Hanqi Li, Alice Fletcher-Etherington, Leah M Hunter, Swati Keshri, Ceri A Fielding, Katie Nightingale, Benjamin Ravenhill, Luis Nobre, Martin Potts, Robin Antrobus, Colin M Crump, David C Rubinsztein, Richard J Stanton, Michael P Weekes

{"title":"Human cytomegalovirus degrades DMXL1 to inhibit autophagy, lysosomal acidification, and viral assembly.","authors":"Hanqi Li, Alice Fletcher-Etherington, Leah M Hunter, Swati Keshri, Ceri A Fielding, Katie Nightingale, Benjamin Ravenhill, Luis Nobre, Martin Potts, Robin Antrobus, Colin M Crump, David C Rubinsztein, Richard J Stanton, Michael P Weekes","doi":"10.1016/j.chom.2024.02.013","DOIUrl":"10.1016/j.chom.2024.02.013","url":null,"abstract":"Human cytomegalovirus (HCMV) is an important human pathogen that regulates host immunity and hijacks host compartments, including lysosomes, to assemble virions. We combined a quantitative proteomic analysis of HCMV infection with a database of proteins involved in vacuolar acidification, revealing Dmx-like protein-1 (DMXL1) as the only protein that acidifies vacuoles yet is degraded by HCMV. Systematic comparison of viral deletion mutants reveals the uncharacterized 7 kDa US33A protein as necessary and sufficient for DMXL1 degradation, which occurs via recruitment of the E3 ubiquitin ligase Kip1 ubiquitination-promoting complex (KPC). US33A-mediated DMXL1 degradation inhibits lysosome acidification and autophagic cargo degradation. Formation of the virion assembly compartment, which requires lysosomes, occurs significantly later with US33A-expressing virus infection, with reduced viral replication. These data thus identify a viral strategy for cellular remodeling, with the potential to employ US33A in therapies for viral infection or rheumatic conditions, in which inhibition of lysosome acidification can attenuate disease.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"466-478.e11"},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytoplasmic calcium influx mediated by plant MLKLs confers TNL-triggered immunity. 由植物 MLKLs 介导的细胞质钙离子流入赋予 TNL 触发的免疫力。

Cell host & microbe Pub Date : 2024-04-10 Epub Date: 2024-03-20 DOI: 10.1016/j.chom.2024.02.016

Qiaochu Shen, Keiichi Hasegawa, Nicole Oelerich, Anna Prakken, Lea Weiler Tersch, Junli Wang, Frowin Reichhardt, Alexandra Tersch, Je Cuan Choo, Ton Timmers, Kay Hofmann, Jane E Parker, Jijie Chai, Takaki Maekawa

{"title":"Cytoplasmic calcium influx mediated by plant MLKLs confers TNL-triggered immunity.","authors":"Qiaochu Shen, Keiichi Hasegawa, Nicole Oelerich, Anna Prakken, Lea Weiler Tersch, Junli Wang, Frowin Reichhardt, Alexandra Tersch, Je Cuan Choo, Ton Timmers, Kay Hofmann, Jane E Parker, Jijie Chai, Takaki Maekawa","doi":"10.1016/j.chom.2024.02.016","DOIUrl":"10.1016/j.chom.2024.02.016","url":null,"abstract":"The plant homolog of vertebrate necroptosis inducer mixed-lineage kinase domain-like (MLKL) contributes to downstream steps in Toll-interleukin-1 receptor domain NLR (TNL)-receptor-triggered immunity. Here, we show that Arabidopsis MLKL1 (AtMLKL1) clusters into puncta at the plasma membrane upon TNL activation and that this sub-cellular reorganization is dependent on the TNL signal transducer, EDS1. We find that AtMLKLs confer TNL-triggered immunity in parallel with RPW8-type HeLo-domain-containing NLRs (RNLs) and that the AtMLKL N-terminal HeLo domain is indispensable for both immunity and clustering. We show that the AtMLKL HeLo domain mediates cytoplasmic Ca2+ ([Ca2+]cyt) influx in plant and human cells, and AtMLKLs are responsible for sustained [Ca2+]cyt influx during TNL-triggered, but not CNL-triggered, immunity. Our study reveals parallel immune signaling functions of plant MLKLs and RNLs as mediators of [Ca2+]cyt influx and a potentially common role of the HeLo domain fold in the Ca2+-signal relay of diverse organisms.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"453-465.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host. 饮食、微生物组和代谢物的对立机制调节易感基因宿主的炎症性肠病。

Cell host & microbe Pub Date : 2024-04-10 Epub Date: 2024-03-20 DOI: 10.1016/j.chom.2024.03.001

Gabriel Vasconcelos Pereira, Marie Boudaud, Mathis Wolter, Celeste Alexander, Alessandro De Sciscio, Erica T Grant, Bruno Caetano Trindade, Nicholas A Pudlo, Shaleni Singh, Austin Campbell, Mengrou Shan, Li Zhang, Qinnan Yang, Stéphanie Willieme, Kwi Kim, Trisha Denike-Duval, Jaime Fuentes, André Bleich, Thomas M Schmidt, Lucy Kennedy, Costas A Lyssiotis, Grace Y Chen, Kathryn A Eaton, Mahesh S Desai, Eric C Martens

{"title":"Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host.","authors":"Gabriel Vasconcelos Pereira, Marie Boudaud, Mathis Wolter, Celeste Alexander, Alessandro De Sciscio, Erica T Grant, Bruno Caetano Trindade, Nicholas A Pudlo, Shaleni Singh, Austin Campbell, Mengrou Shan, Li Zhang, Qinnan Yang, Stéphanie Willieme, Kwi Kim, Trisha Denike-Duval, Jaime Fuentes, André Bleich, Thomas M Schmidt, Lucy Kennedy, Costas A Lyssiotis, Grace Y Chen, Kathryn A Eaton, Mahesh S Desai, Eric C Martens","doi":"10.1016/j.chom.2024.03.001","DOIUrl":"10.1016/j.chom.2024.03.001","url":null,"abstract":"Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis. Inflammation starts with the expansion of natural killer cells and altered immunoglobulin-A coating of some bacteria. Lethal colitis is then driven by Th1 immune responses to increased activities of mucin-degrading bacteria that cause inflammation first in regions with thinner mucus. A fiber-free exclusive enteral nutrition diet also induces mucus erosion but inhibits inflammation by simultaneously increasing an anti-inflammatory bacterial metabolite, isobutyrate. Our findings underscore the importance of focusing on microbial functions-not taxa-contributing to IBDs and that some diet-mediated functions can oppose those that promote disease.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"527-542.e9"},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11064055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A specific enterotype derived from gut microbiome of older individuals enables favorable responses to immune checkpoint blockade therapy. 从老年人肠道微生物组中提取的特异性肠型可对免疫检查点阻断疗法产生良好反应。

Cell host & microbe Pub Date : 2024-04-10 Epub Date: 2024-03-20 DOI: 10.1016/j.chom.2024.03.002

Xiaoqiang Zhu, Xiaowen Huang, Muni Hu, Rongrong Sun, Jiantao Li, Hai Wang, Xuefeng Pan, Yanru Ma, Lijun Ning, Tianying Tong, Yilu Zhou, Jinmei Ding, Ying Zhao, Baoqin Xuan, Jing-Yuan Fang, Jie Hong, Jason Wing Hon Wong, Youwei Zhang, Haoyan Chen

{"title":"A specific enterotype derived from gut microbiome of older individuals enables favorable responses to immune checkpoint blockade therapy.","authors":"Xiaoqiang Zhu, Xiaowen Huang, Muni Hu, Rongrong Sun, Jiantao Li, Hai Wang, Xuefeng Pan, Yanru Ma, Lijun Ning, Tianying Tong, Yilu Zhou, Jinmei Ding, Ying Zhao, Baoqin Xuan, Jing-Yuan Fang, Jie Hong, Jason Wing Hon Wong, Youwei Zhang, Haoyan Chen","doi":"10.1016/j.chom.2024.03.002","DOIUrl":"10.1016/j.chom.2024.03.002","url":null,"abstract":"Immunotherapy has revolutionized cancer treatment, but inconsistent responses persist. Our study delves into the intriguing phenomenon of enhanced immunotherapy sensitivity in older individuals with cancers. Through a meta-analysis encompassing 25 small-to-mid-sized trials of immune checkpoint blockade (ICB), we demonstrate that older individuals exhibit heightened responsiveness to ICB therapy. To understand the underlying mechanism, we reanalyze single-cell RNA sequencing (scRNA-seq) data from multiple studies and unveil distinct upregulation of exhausted and cytotoxic T cell markers within the tumor microenvironment (TME) of older patients. Recognizing the potential role of gut microbiota in modulating the efficacy of immunotherapy, we identify an aging-enriched enterotype linked to improved immunotherapy outcomes in older patients. Fecal microbiota transplantation experiments in mice confirm the therapeutic potential of the aging-enriched enterotype, enhancing treatment sensitivity and reshaping the TME. Our discoveries confront the prevailing paradox and provide encouraging paths for tailoring cancer immunotherapy strategies according to an individual's gut microbiome profile.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"489-505.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plant cellular messengers mobilized to defend. 调动植物细胞信使进行防御。

Cell host & microbe Pub Date : 2024-03-13 DOI: 10.1016/j.chom.2024.02.005

Lifan Sun, Jie Zhang

引用次数: 0

Alistipes indistinctus-derived hippuric acid promotes intestinal urate excretion to alleviate hyperuricemia. 茜草提取的马尿酸能促进肠道尿酸盐排泄，从而缓解高尿酸血症。

Cell host & microbe Pub Date : 2024-03-13 Epub Date: 2024-02-26 DOI: 10.1016/j.chom.2024.02.001

Ying-Xi Xu, Lu-Di Liu, Jiang-Yuan Zhu, Shan-Shan Zhu, Bing-Qi Ye, Jia-Lu Yang, Jing-Yi Huang, Zhi-Hao Huang, Yi You, Wen-Kang Li, Jia-Lin He, Min Xia, Yan Liu

{"title":"Alistipes indistinctus-derived hippuric acid promotes intestinal urate excretion to alleviate hyperuricemia.","authors":"Ying-Xi Xu, Lu-Di Liu, Jiang-Yuan Zhu, Shan-Shan Zhu, Bing-Qi Ye, Jia-Lu Yang, Jing-Yi Huang, Zhi-Hao Huang, Yi You, Wen-Kang Li, Jia-Lin He, Min Xia, Yan Liu","doi":"10.1016/j.chom.2024.02.001","DOIUrl":"10.1016/j.chom.2024.02.001","url":null,"abstract":"Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"366-381.e9"},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conquering homocystinuria with engineered probiotics. 用工程益生菌战胜高胱氨酸尿症。

Cell host & microbe Pub Date : 2024-03-13 DOI: 10.1016/j.chom.2024.02.008

Skye R S Fishbein, Esse M Evbuomwan, Gautam Dantas

引用次数: 0

A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection. 一种保守抗原可诱导呼吸道 Th17 介导的广泛血清型保护，防止肺炎球菌超级感染。

Cell host & microbe Pub Date : 2024-03-13 Epub Date: 2024-02-27 DOI: 10.1016/j.chom.2024.02.002

Xue Liu, Laurye Van Maele, Laura Matarazzo, Daphnée Soulard, Vinicius Alves Duarte da Silva, Vincent de Bakker, Julien Dénéréaz, Florian P Bock, Michael Taschner, Jinzhao Ou, Stephan Gruber, Victor Nizet, Jean-Claude Sirard, Jan-Willem Veening

{"title":"A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection.","authors":"Xue Liu, Laurye Van Maele, Laura Matarazzo, Daphnée Soulard, Vinicius Alves Duarte da Silva, Vincent de Bakker, Julien Dénéréaz, Florian P Bock, Michael Taschner, Jinzhao Ou, Stephan Gruber, Victor Nizet, Jean-Claude Sirard, Jan-Willem Veening","doi":"10.1016/j.chom.2024.02.002","DOIUrl":"10.1016/j.chom.2024.02.002","url":null,"abstract":"Several vaccines targeting bacterial pathogens show reduced efficacy upon concurrent viral infection, indicating that a new vaccinology approach is required. To identify antigens for the human pathogen Streptococcus pneumoniae that are effective following influenza infection, we performed CRISPRi-seq in a murine model of superinfection and identified the conserved lafB gene as crucial for virulence. We show that LafB is a membrane-associated, intracellular protein that catalyzes the formation of galactosyl-glucosyl-diacylglycerol, a glycolipid important for cell wall homeostasis. Respiratory vaccination with recombinant LafB, in contrast to subcutaneous vaccination, was highly protective against S. pneumoniae serotypes 2, 15A, and 24F in a murine model. In contrast to standard capsule-based vaccines, protection did not require LafB-specific antibodies but was dependent on airway CD4+ T helper 17 cells. Healthy human individuals can elicit LafB-specific immune responses, indicating LafB antigenicity in humans. Collectively, these findings present a universal pneumococcal vaccine antigen that remains effective following influenza infection.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"304-314.e8"},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0